Allergen-specific Immunotherapy In Asthma Research Articles

ДЛИТЕЛЬНОСТЬ КЛИНИЧЕСКОГО ЭФФЕКТА НИЗКОДОЗОВОЙ СУБЛИНГВАЛЬНО-ПЕРОРАЛЬНОЙ АЛЛЕРГЕНСПЕЦИФИЧЕСКОЙ ИММУНОТЕРАПИИ БРОНХИАЛЬНОЙ АСТМЫ

Background. Allergen-specific immunotherapy (ASIT) affects the immune response and the clinical course of bronchial asthma (BA). Objective. To evaluate the clinical efficacy of sublingual-oral low-dose ASIT in asthma based on the results of 5-year follow-up. Material and Methods. ASIT was carried out with a mixture of household allergens in 51 patients aged 18-60 years old. The patient's opinion, the number and severity of BA exacerbations, the duration of post-immunotherapeutic remission and the factors influencing it, adherence to treatment, and the safety of treatment were taken into account. Results. The effectiveness of ASIT according to the patient’s opinion: 45.1% - excellent, 49% - good result. In allergic asthma, remission after ASIT was significantly higher than in mixed asthma. Full adherence to treatment (3 courses of ASIT) - in 76.5% (39/51) of patients. There were no adverse reactions during the entire observation period. The mixed BA phenotype, contact with the allergen in everyday life, and smoking had a negative effect. Positive - high compliance to therapy. Conclusions. Sublingual-oral ASIT is an effective and safe method of treating allergic and mixed asthma. The duration of post-immunotherapeutic remission of BA for 3 years was observed after 3 courses of ASIT.

Safety, Efficacy, and Preventive Role of Subcutaneous and Sublingual Allergen Immunotherapy for the Treatment of Pediatric Asthma.

Allergen-specific immunotherapy is currently the only treatment with the potential to modify and prevent progression of allergic asthma in children. In clinical practice, it is available in two forms: subcutaneous immunotherapy and sublingual immunotherapy. Trials and meta-analyses showed both the safety and the short- and long-term benefits of allergen-specific immunotherapy in asthmatic children. However, its use and role in asthma remains controversial, since studies are largely heterogeneous. This is mainly due to the lack of consensus on the optimal primary outcome to be considered for clinical trials evaluating the efficacy of allergen-specific immunotherapy in asthma. Therefore, well-conducted researchis needed using standardized and validated tools to evaluate key outcomes in asthmatic children.

Tryptophan metabolite-regulated Treg responses contribute to attenuation of airway inflammation during specific immunotherapy in a mouse asthma model

ABSTRACT In allergen-specific immunotherapy for asthma, antigens attached to dendritic cells increase the tryptophan metabolism in these cells and alter the Th17/Treg balance in the airways. Tryptophan metabolism has long been suggested to be relevant in the pathophysiology of allergic disorders, including asthma. Our study investigated whether tryptophan metabolites are responsible for the changes in Th17/Treg balance and decreases in airway hyperreactivity and inflammation seen during allergen-specific immunotherapy in an asthma model. Ovalbumin was injected intraperitoneally into mice to establish an asthma model, and then high dose ovalbumin allergen-specific immunotherapy was administered to induce immune tolerance. Airway hyperreactivity and serum ovalbumin-specific immunoglobulin E were measured to assess whether the animal model was successfully established. We then examined the influence of inhibition of tryptophan metabolism and the addition of tryptophan metabolites on allergen-specific immunotherapy-induced changes in the Th17/Treg balance and decreases in airway inflammation and inflammatory cytokines. Production of tryptophan metabolites was partly responsible for the allergen-specific immunotherapy-induced increase in Tregs, decrease in airway inflammation, and decrease in inflammatory cytokines. Ovalbumin-specific immunoglobulin E and airway hyperreactivity were not affected. In the context of asthma, an increase in tryptophan metabolites is one of the mechanisms by which allergen-specific immunotherapy achieves immune tolerance.

Subcutaneous and Sublingual Immunotherapy in a Mouse Model of Allergic Asthma.

Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath. Allergen specific immunotherapy (AIT) is the only treatment that is capable of modifying the immunological process underlying allergic responses including allergic asthma and both subcutaneous AIT (SCIT) as well as sublingual AIT (SLIT) have proven clinical efficacy in long term suppression of the allergic response. Although these treatments are very successful for rhinitis, application of AIT in asthma is hampered by variable efficacy, long duration of treatment, and the risk of severe side-effects. A more profound understanding of the mechanisms by which AIT achieves tolerance to allergens in sensitized individuals is needed to improve its efficacy. Mouse models have been very valuable as a preclinical model to characterize the mechanisms of desensitization in AIT and to evaluate novel approaches for improved efficacy. Here, we present a rapid and reproducible mouse model for allergen-specific immunotherapy. In this model, mice are sensitized with two injections of allergen absorbed to aluminum hydroxide to induce allergic sensitization, followed by subcutaneous injections (SCIT) or sublingual administrations (SLIT) of the allergen as immunotherapy treatment. Finally, mice are challenged by three intranasal allergen administrations. We will describe the protocols as well as the most important read-out parameters including measurement of invasive lung function measurements, serum immunoglobulin levels, isolation of broncho-alveolar lavage fluid (BALF), and preparation of cytospins. Moreover, we describe how to restimulate lung single cell suspensions, perform flow cytometry measurements to identify populations of relevant immune cells, and perform ELISAs and Luminex assays to measure the cytokine concentrations in BALF and lung tissue.

Cockroach allergy and allergen-specific immunotherapy in asthma: potential and pitfalls.

To provide a summary and discussion of cockroach allergy and clinical trials of cockroach allergen immunotherapy. Cockroach allergen exposure among sensitized children is increasingly recognized as a key factor contributing to asthma morbidity. Recent trials suggest that cockroach immunotherapy holds promise as a treatment strategy with studies demonstrating immunomodulatory and clinical effects. However, a few obstacles need to be overcome to realize the full potential of this treatment modality as cockroach-allergic patients often exhibit complex sensitization patterns to multiple cockroach-associated proteins, and an immunodominant allergen has not been identified. These factors have made it difficult to produce standardized cockroach allergen extracts that are potent and provide the broad allergen profiles needed for optimal treatment. There have been important advances in the identification and cloning of cockroach allergens, and several strategies are being developed to provide therapeutic cockroach allergen products with enhanced clinical efficacy. Allergen immunotherapy has the capability of modulating the immune response to cockroach allergen and has potential as a valuable treatment modality. Further studies of the clinical efficacy, along with the development of improved therapeutic products, are needed to advance our knowledge and realize the full potential of this promising therapy.

Allergen Specific Immunotherapy in Asthma

The use of allergen Specific Immunotherapy (SIT) to treat allergic asthma is still a matter of scientific debate. Currently, there are few studies specifically designed to evaluate asthma, and few studies had a formal sample size calculation, or objective parameters of pulmonary function assessed. On the other hand, there are good quality trials with both Subcutaneous Immuno-therapy (SCIT) and Sublingual Immunotherapy (SLIT) in allergic rhinitis, where asthma symptoms were also evaluated, if present. These studies consistently reported positive results. Moreover, several favourable meta-analyses are available, although their validity is limited by the great heterogeneity of the trials included. The disease modifying effect of SIT that is the capacity of preventing asthma onset should be also taken into account. Concerning the safety, fatalities seem to be an exceptional event, and in Europe no fatality has been reported over the last two decades. Uncontrolled asthma is universally recognized as the most important risk factor for severe adverse events. In conclusion, both SLIT and SCIT can be used in asthma associated with rhinitis (which is the most common condition), provided that asthma is adequately controlled by pharmacotherapy. In such case, a measurable clinical benefit on asthma symptoms can be expected. Nonetheless, SIT cannot be presently recommended as single therapy when asthma is the unique manifestation of respiratory allergy.

Injection allergen immunotherapy for asthma

Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and methods of delivery, we updated the systematic review of allergen specific immunotherapy for asthma. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. We searched the Cochrane Airways Group Trials Register up to 2005, Dissertation Abstracts and Current Contents. Randomised controlled trials using various forms of allergen specific immunotherapy to treat asthma and reporting at least one clinical outcome. Three authors independently assessed eligibility of studies for inclusion. Two authors independently performed quality assessment of studies. Eighty-eight trials were included (13 new trials). There were 42 trials of immunotherapy for house mite allergy; 27 pollen allergy trials; 10 animal dander allergy trials; two Cladosporium mould allergy, two latex and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 16 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication, and improvement in bronchial hyper-reactivity following immunotherapy. There was a significant improvement in asthma symptom scores (standardised mean difference -0.59, 95% confidence interval -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI 3 to 5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall it would have been necessary to treat four patients (95% CI 3 to 6) with immunotherapy to avoid one requiring increased medication. Allergen immunotherapy significantly reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. If 16 patients were treated with immunotherapy, one would be expected to develop a local adverse reaction. If nine patients were treated with immunotherapy, one would be expected to develop a systemic reaction (of any severity). Immunotherapy reduces asthma symptoms and use of asthma medications and improves bronchial hyper-reactivity. One trial found that the size of the benefit is possibly comparable to inhaled steroids. The possibility of local or systemic adverse effects (such as anaphylaxis) must be considered.

Current place of allergen-specific immunotherapy in asthma and rhinitis

Immunotherapy is considered a controversial treatment of allergic diseases in spite of a documented clinical relevant efficacy in controlled studies investigating Hymenoptera allergy, allergic rhinitis and asthma. The guidelines as to the use of immunotherapy have been provided in several international position papers. Immunotherapy is recommended in patients with an unequivocal IgE-mediated disease not responding adequately to allergen avoidance and with a need for prophylactic topical corticosteroids for longer periods (season or perennially). The clinical benefit in relation to reducing the need for drugs, and potential preventive aspects of immunotherapy should be carefully weighted against the risk of the disease and therapeutic injections. Immunotherapy should only be initiated with allergens that in controlled studies have documented both clinical efficacy and safety. Immunotherapy is recommended as a supplement to pharmacotherapy to interfere broadly in the pathophysiological mechanisms of the allergic inflammation by a multifactorial treatment approach. Le traitement des maladies allergiques par l'immunothérapie reste un sujet controversé en dépit d'une efficacité clinique documentée par des études contrôlées portant sur l'allergie aux hyménoptères, la rhinite allergique et l'asthme. Les directives sur l'emploi de l'immunothérapie ont été définies dans plusieurs prises de position internationales. L'immunothérapie est conseillée chez les patients dont la maladie est sans nul doute médiée par IgE, ne répond pas à une élimination correcte de l'allergène et nécessite une prophylaxie par corticostéroïdes topiques pour de longues périodes (saisonnières ou perannuelles). Le bénéfice clinique lié à la réduction du besoin de médicaments et l'aspect préventif potentiel de l'immunothérapie doivent être soigneusement évalués face aux risques de la maladie et des injections nécessaires au traitement. L'immunothérapie ne doit être mise en œuvre qu'avec des allergènes dont des études contrôlées ont montré à la fois l'efficacité et l'innocuité. L'immunothérapie est recommandée comme complément de la pharmacothérapie pour entraver, au sens large, les mécanismes physiopathologiques de l'inflammation allergique par une approache thérapeutique multifactorielle.